Without blood flow, bone cannot maintain its integrity. Bone blood flow responds to various local and systemic factors, however, bone perfusion in humans remains relatively unstudied. We will investigate key mechanisms that regulate bone perfusion in able-bodied and contrast responses to those with spinal cord injury (SCI). SCI is a model of chronic reduced loading with loss of sympathetic regulation. In tibial cortical bone, we will: 1) determine the impact of compressive loading with and without muscle contractions; 2) determine the impact of vascular sympathetic activity and systemic perfusion pressure; 3) compare the response between able- bodied and those with SCI. Acute metabolic needs of bone due to loading increase flow substantially. In addition, the bone vasculature is innervated by a rich network of sympathetic nerves that serve a functional purpose in the control of blood flow. A critical limitation to the study of bone blood flow in humans has been the lack of non-invasive assessments. We developed a near infrared spectroscopy (NIRS) device to non-invasively assess blood content in bone and assessed tibial perfusion in response to exercise. Here, we will test the hypothesis that bone blood flow increases proportional to loading conditions in both able-bodied individuals and those with SCI. We will also test the hypothesis that there are decreases in blood bone flow that are proportional to increases in leg vascular sympathetic outflow in the able-bodied, but that changes in bone blood flow are proportional to changes in blood pressure in those with SCI. The proposed research will be some of the first to determine the control of bone flow in humans.